Morphological and structural characteristics of the proximal femur in human and rat
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Cancellous bone
Periosteum
Biomechanics
ABSTRACT Strain magnitude has a controlling influence on bone adaptive response. However, questions remain as to how and if cancellous and cortical bone tissues respond differently to varied strain magnitudes, particularly at a molecular level. The goal of this study was to characterize the time‐dependent gene expression, bone formation, and structural response of the cancellous and cortical bone of female C57Bl/6 mice to mechanical loading by applying varying load levels (low: −3.5 N; medium: −5.2 N; high: −7 N) to the skeleton using a mouse tibia loading model. The loading experiment showed that cortical bone mass at the tibial midshaft was significantly enhanced following all load levels examined and bone formation activities were particularly elevated at the medium and high loads applied. In contrast, for the proximal metaphyseal cancellous bone, only the high load led to significant increases in bone mass and bone formation indices. Similarly, expression of genes associated with inhibition of bone formation (e.g., Sost ) was altered in the diaphyseal cortical bone at all load levels, but in the metaphyseal cortico‐cancellous bone only by the high load. Finite element analysis determined that the peak tensile or compressive strains that were osteogenic for the proximal cancellous bone under the high load were significantly greater than those that were osteogenic for the midshaft cortical tissues under the low load. These results suggest that the magnitude of the strain stimulus regulating structural, cellular, and molecular responses of bone to loading may be greater for the cancellous tissues than for the cortical tissues. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Mechanical load
Strain (injury)
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Several parameters of bone mass and function were investigated in three experiments involving intact, ovariectomized, or hormone-supplemented ovariectomized female cynomolgus monkeys. Ovariectomized animals had increased serum levels of alkaline phosphatase and acid phosphatase compared with intact and hormone-supplemented animals. Vertebral bone mass measured ex vivo by dual-photon absorptiometry was reduced by 11-19% in ovariectomized animals compared with intact and hormone-supplemented animals. The most dramatic effects observed with ovariectomy were markedly increased (30-60%) bone formation rates in vertebral cancellous bone, primarily caused by higher activation frequency of basic multicellular units of bone. In addition, combined resorption and reversal periods were decreased and formation period increased in untreated ovariectomized animals. Changes in static histomorphometry parameters were less dramatic, cancellous bone volume being 1-14% lower in ovariectomized animals compared with intact or ovariectomized hormone-supplemented animals. The data indicate that changes in bone resorption are primarily responsible for the lower bone mass of estrogen deficiency and increased bone mass in hormone-supplemented animals. Bone changes in ovariectomized cynomolgus monkeys resemble those in women after menopause and similarly respond positively to hormone supplementation. As such, cynomolgus monkeys are an excellent model for studying the basic mechanisms of osteoporosis and for the development of suitable therapeutic regimens.
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There are substantial changes in maternal skeletal dynamics during pregnancy, lactation, and after lactation. The purpose of this study was to correlate changes in cortical and cancellous bone mass, structure, and dynamics with mechanical properties during and after the first reproductive cycle in rats. Rats were mated and groups were taken at parturition, end of lactation and 8 wk after weaning, and were compared with age-matched, nulliparous controls. Measurements were taken on femoral cortical bone and lumbar vertebral body cancellous bone. At the end of pregnancy, there was an increase in cortical periosteal bone formation and an increase in cortical volume, but a suppression of turnover in cancellous bone with no change in cancellous or cortical mechanical properties. Lactation was associated with a decrease in cortical and cancellous bone strength with a decrease in bone volume, but an increase in turnover on cancellous and endocortical surfaces. After lactation, there was a partial or full restoration of mechanical properties. This study demonstrates substantial changes in bone mechanics that correlate with changes in bone structure and dynamics during the first reproductive cycle in rats. The greatest changes were observed during the lactation period with partial or full recovery in the postlactational period.
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Bone remodeling
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Abstract The vertebrate skeleton is an adaptive structure that responds to mechanical stimuli by increasing bone mass under increased mechanical loads. Although experimental animal models have shown the anabolic cortical bone response to applied load decreases with age, no consensus exists regarding whether this adaptive mechanism is affected by age in cancellous bone, the tissue most impacted by age-related bone loss. We used an established murine in vivo tibial loading model to characterize the load-induced cancellous, cortical, and whole bone responses to mechanical stimuli in growing and mature female mice at 6, 10, and 16wks of age. The effects of applied load on tibial morphology and stiffness were determined using microcomputed tomography and in vivo bone strains measured at the medial tibial midshaft during applied loading. At all ages, two weeks of applied load produced larger midshaft cortical cross-sectional properties (+13-72%) and greater cancellous bone volume (+21-107%) and thicker trabeculae (+31-68%) in the proximal metaphyses of the loaded tibiae. The relative anabolic response decreased from 6wks to 16wks of age in both the cancellous and cortical envelopes. Load-induced tibial stresses decreased more in 6wk old mice following loading, which corresponded to increased in vivo tibial stiffness. Stiffness in the loaded tibiae of 16wk old mice decreased despite moderately increased cortical cross-sectional geometry, suggesting load-induced changes in bone material properties. This study shows that the cancellous and cortical anabolic responses to mechanical stimuli decline with age into adulthood and that cortical cross-sectional geometry alone does not necessarily predict whole bone functional stiffness.
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Mechanical load
X-ray microtomography
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Abstract As a daily physiological mechanism in bone, microdamage accumulation dissipates energy and helps to prevent fractures. However, excessive damage accumulation might bring adverse effects to bone mechanical properties, which is especially problematic among the osteoporotic and osteopenic patients treated by bisphosphonates. Some pre-clinical studies in the literature applied forelimb loading models to produce well-controlled microdamage in cortical bone. Ovariectomized animals were also extensively studied to assimilate human conditions of estrogen-related bone loss. In the present study, we combined both experimental models to investigate microdamage accumulation in the context of osteopenia and zoledronate treatment. Three-month-old normal and ovariectomized rats treated by saline or zoledronate underwent controlled compressive loading on their right forelimb to create in vivo microdamage, which was then quantified by barium sulfate contrast-enhanced micro-CT imaging. Weekly in vivo micro-CT scans were taken to evaluate bone (re)modeling and to capture microstructural changes over time. After sacrifice, three-point-bending tests were performed to assess bone mechanical properties. Results show that the zoledronate treatment can reduce cortical microdamage accumulation in ovariectomized rats, which might be explained by the enhancement of several bone structural properties such as ultimate force, yield force, cortical bone area and volume. The rats showed increased bone formation volume and surface after the generation of microdamage, especially for the normal and the ovariectomized groups. Woven bone formation was also observed in loaded ulnae, which was most significant in ovariectomized rats. Although all the rats showed strong correlations between periosteal bone formation and microdamage accumulation, the correlation levels were lower for the zoledronate-treated groups, potentially because of their lower levels of microdamage. The present study provides insights to further investigations of pharmaceutical treatments for osteoporosis and osteopenia. The same experimental concept can be applied in future studies on microdamage and drug testing.
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Osteopenia
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Two hundred SD rats were divided into three groups: ovariectomized, ovariectomized plus estradiol treatment and Sham-operated. The preventive and therapeutic effect of the low-dose 17β estradiol on cancellous bone loss in overiectomized rats was found.
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Cancellous bone
Biomechanics
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AIM: To discuss the influence of selective estrogen receptor modulator(SERM) raloxifene(RAL) on the expression of TNF-α in cancellous bone and bone mineral density (BMD) loss in ovariectomized rats. METHODS: Thirty 8-month nulliparous female SD rats were divided into 3 groups(10 rats per group):sham operation (SHAM)group, ovariectomized (OVX)group and therapeutic (OVX+ RAL)group. Bilateral ovariectomies were done on OVX group and OVX+ RAL group. Sham operation was performed on SHAM group. OVX+ RAL group was treated with RAL 2 d after operation. Twenty weeks after operation, all rats were sacrificed.BMD of L3-L5 vertebrae, proximal femoral segment, femoral body were measured by dual energy X-ray absorptiometry(DEXA). SABC immunohistochemistry and image analysis were used to detect the expression of TNF-α in L2 vertebral bone of every group. RESULTS: ① The gray scale of TNF-α in cancellous bone in OVX group was lower than that in SHAM group (P0.01), and also lower than that in OVX+ RAL group (P0.01), indicating that the expression of TNF-α in cancellous bone in OVX group increased after ovariectomy, and became weak after RAL treatment. ② Twenty weeks after ovariectomy, BMD of L3-L5 vertebrae, proximal femoral segment, femoral body of ovariectomized rats decreased significantly and the trabecular bone became thinner and irregular as compared with SHAM group(P0.01). After treatment of RAL, the above parameters were maintained close to the level of SHAM group (P0.05). CONCLUSION: RAL could inhibit the expression of TNF-α in cancellous bone of ovariectomized rats and depress the occurrence of osteoporosis in ovariectomized rats.
Cancellous bone
Raloxifene
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